The Outcomes of Subxiphoid Thoracoscopic Versus Video-Assisted Thoracic Surgery for Thymic Diseases

Abstract

Objectives:

The subxiphoid thoracoscopic approach may be an alternative to the lateral transthoracic approach in the treatment of thymic diseases. This study aimed to assess the safety and efficacy of subxiphoid video-assisted thoracoscopic surgery and compare this approach with the lateral transthoracic variation in terms of short-term perioperative outcomes.

Methods:

Data for 107 consecutive adult patients who underwent transthoracic or subxiphoid video-assisted thoracic surgery for thymic diseases from July 2015 to February 2019 were retrospectively reviewed. The patients were stratified according to whether they had accompanying myasthenia gravis (MG). Perioperative outcomes were compared between the two cohorts.

Results:

A total of 107 patients were identified, including 37 patients who underwent subxiphoid video-assisted thoracoscopic thymectomy (S-VATT) and 70 patients who underwent transthoracic video-assisted thoracoscopic thymectomy (T-VATT). The S-VATT group exhibited less operative blood loss (112.14 ± 117.01 versus 58.81 ± 48.67, P = .003), a shorter duration of chest tube usage (3.77 ± 1.83 versus 2.18 ± 1.88, P = .000), lower postoperative pain scores (4.99 ± 0.99 versus 1.57 ± 0.55, P = .000), and a shorter length of postoperative hospital stay (5.83 ± 1.38 versus 4.38 ± 1.26, P = .000) than the T-VATT group. For MG patients, the median operative time was significantly shorter in the S-VATT group than in the T-VATT group (141.46 ± 54.17 versus 95.63 ± 31.25, P = .004).

Conclusions:

S-VATT is a safe approach for patients with thymic diseases and has potential advantages of a shorter operative time, less intraoperative bleeding, and less postoperative pain compared with the lateral transthoracic approach, especially for patients with MG.

Introduction

Minimally invasive surgical techniques play a very important role in the surgical management of thymic tumors. Video-assisted thoracoscopic thymectomy (VATT) is currently a popular surgical procedure with several advantages, including low postoperative pain levels, few perioperative complications, small surgical incisions, and short hospital stays.^1–3 However, conventional lateral transthoracic approaches have some drawbacks, such as poor visualization of the mediastinal fat and contralateral phrenic nerve, intercostal nerve impairment, and difficulty in resecting the upper pole of the thymus.^4–6

The ideal approach for thymectomy should include adequate exposure of the entire anterior mediastinum to facilitate resection of all of the thymic tissue and mediastinal fat. The subxiphoid approach can provide a good surgical view of the entire thymus and bilateral phrenic nerves to easily achieve an extended thymectomy. We performed the three-portal “subxiphoid and subcostal arch” approach, which was first reported by Zhou et al. in 2017.⁷ This approach avoids instrument interference and the need for special devices. Herein, we present our experiences with subxiphoid video-assisted thoracoscopic thymectomy (S-VATT) and analyze its benefits in terms of perioperative outcomes through comparison with transthoracic lateral approaches.

Materials and Methods

Patients

This retrospective study was approved by the Ethics Committee of the Second Affiliated Hospital of Harbin Medical University. Data from consecutive adult patients who underwent VATT from July 2015 to February 2019 at our institution were reviewed.

Routine preoperative evaluations include electrocardiograms, ultrasound cardiograms, pulmonary function tests, and laboratory examinations. Contrast-enhanced computed tomography (CT) scanning was performed to evaluate thymic tumors. The indications for VATT include Masaoka stage I–II thymomas (<5 cm in diameter), hyperplasia of the thymus gland with myasthenia gravis (MG), and thymic cysts (indistinguishable from thymoma). If the patients experienced MG symptoms, neurological assessments were performed by neurologists.

Ultimately, a total of 107 patients were identified, including 37 who underwent S-VATT and 70 who underwent transthoracic video-assisted thoracoscopic thymectomy (T-VATT). The operations were performed by 3 surgeon groups. The decision to use a subxiphoid or transthoracic approach was according to the individual surgeon's discretion. Patient demographics, surgical procedure parameters, pathological diagnosis, perioperative complications, and outcomes were collected and compared.

Surgical technique

Subxiphoid video-assisted thoracoscopic thymectomy

The patients were placed in a supine position on the operating table, with the surgeon positioned between the patient's legs. Mechanical ventilation was provided using a single-lumen endotracheal tube with the patient under general anesthesia. A 3-cm skin incision was made ∼1 cm below the xiphoid. We established the subxiphoid approach with a self-created balloon.⁸ The balloon was completely inserted into the retrosternal space, after which 600–800 mL of air was injected into the balloon using a syringe. The balloon was maintained inflated for 5 minutes, deflated, and removed. Two 5-mm ports were created at the midclavicular line intersecting with the bilateral costal arches under the guidance of the surgeon's finger. A 30°, a 10-mm thoracoscope was placed through the established subxiphoid incision. CO₂ insufflation of the mediastinum was initiated at 8 mmHg. An atraumatic grasper and ultrasonic harmonic scalpel (Ethicon Endo-Surgery, Cincinnati, OH) were introduced into the 5-mm ports.

First, the mediastinal pleura was opened to expose the bilateral thoracic cavities. The lower poles of the thymus were mobilized from the pericardium and ascending aorta. The bilateral phrenic nerves were exposed and the pleural nerve was cut at a 5-mm distance from the phrenic nerves, and the left innominate vein was carefully exposed from the junction of the superior vena cava and innominate vein. There are usually several thymic veins that join together into the innominate, and the ultrasonic scalpel can safely seal these thymic veins. The bilateral upper poles of the thymus were easily dissected by the ultrasonic scalpel. In addition, we followed the “tumor last” principle for thymoma resection, whereby the normal part of the thymus was always dissected first to minimize the risk of pleural dissemination. For MG patients, all fat pads were harvested using the harmonic scalpel. The pre-pericardial fat pads and fat pads in the cardiac-diaphragmatic angles and aortopulmonary window were carefully dissected and removed. Once the surgery was completed, the specimen was removed in its entirety with the surrounding fatty tissue and retrieved in a bag from the subxiphoid incision. An 18F chest tube was routinely placed in both pleural cavities. The thymomas confirmed by pathology were stratified according to their Masaoka–Koga stage⁹ and World Health Organization histological classifications.¹⁰

Transthoracic video-assisted thoracoscopic thymectomy

The patients were intubated with a double-lumen endotracheal tube. A right-sided 45° semisupine position was adopted, and the right arm of the patient was extended to expose the axilla field. The first incision was made at the fifth intercostal space, with a posterior axillary line serving as the camera port. To serve as operative ports, two additional 5-mm ports were made at the third intercostal space, anterior axillary line, and at the fifth intercostal space, middle clavicular line. The superior poles of the thymus were completely dissected away from the neck. The thymic veins that joined into the left innominate vein were identified and divided. After resection, the thymus and surrounding fat tissues were retrieved. An 18F chest tube was routinely placed in both pleural cavities.

After the operation, all patients stayed in the postanesthesia care unit for 1–2 hours before being moved to the thoracic surgery wing. Postoperative analgesia with intravenous flurbiprofen axetil (50 mg bid) was given. Pain scores were evaluated by nurses using a visual analogue scale (VAS: 0 is completely pain free and 10 is the worst pain imaginable). These scores were documented for the first time on the same day of surgery and then every postoperative day until discharge. The chest tubes were removed if the drainage volume was <100 mL with no air leakage. Patients who were able to mobilize independently and had normal chest radiographs were discharged after chest tube removal.

The Myasthenia Gravis Foundation of America (MGFA) classification and Quantitative Myasthenia Gravis (QMG) score were used to evaluate the severity of MG. To assess the effect of the two approaches, we compared the postoperative MG-QMG score and dose reduction of cholinesterase inhibitors at 3 months postoperatively. All patients completed the follow-up (the last follow-up was in April 2019) with a routine clinical evaluation. Chest CT scans were required for thymoma patients every 6 months during the first 2 years after surgery and then every year thereafter.

Continuous variables are expressed as the mean and standard deviation. Variables were compared using independent two-sample t-tests or Mann–Whitney U tests, and one-way analysis of variance was employed to compare more than two groups. Categorical variables are expressed as percentages. We evaluated the independence of the categorical variables using Fisher's exact test. All statistical analyses were performed using SPSS software (SPSS version 24.0; IBM Corp., Armonk, NY), and P < .05 was considered statistically significant.

Results

From July 2015 to February 2019, 37 patients underwent S-VATT and were included for analysis; 70 patients underwent T-VATT. Thirty-seven (34.6%) and 70 (65.4%) patients were diagnosed with thymoma and non-thymoma diseases, respectively. There were 44 (41.1%) and 67 (59.9%) MG and non-MG cases, respectively. There were no differences in age, sex, comorbidities, smoking status, pulmonary function, tumor size, or pathologic diagnosis between the S-VATT and T-VATT patients (Table 1). The median length of follow-up was different between the two groups (P = .004), with a median period of 32.6 ± 14.6 months in the T-VATT group compared to a median length of 16.5 ± 10.4 months in the S-VATT group (Table 1). During follow-up, only 1 patient in the T-VATT group had a thymoma recurrence, at 2 years after the surgery.

Table 1.

Characteristics and Pathological Data of Patients

Variable	T-VATT (n = 70)	S-VATT (n = 37)	P
Age (years)	49.06 ± 13.58	53.05 ± 12.03	.13
Male/female	32/38	19/18
Height (cm)	164.10 ± 8.26	166.16 ± 8.10	.94
Weight (kg)	66.10 ± 15.45	68.76 ± 15.45	.48
Myasthenia gravis/non-myasthenia gravis	28/42	16/21	.84
Pulmonary function tests
FEV1 (L)	2.50 ± 0.61	2.57 ± 0.74	.61
FEV1 (%)	89.95 ± 18.89	89.55 ± 15.68	.91
Comorbidity	17 (24.3%)	11 (29.8%)
COPD	4	4
Heart disease	6	3
HTA diabetes mellitus	7	4
Current smoker	29	18
Thymoma/non-thymoma	29/41	8/29	.054
Masaoka stage			.644
I	10	3
II	19	6
WHO type			.536
A	4	3
AB	9	2
B1	7	2
B2	5	1
B3	4	0
Lesion diameter (mm)	34.95 ± 22.19	37.30 ± 22.45	.77
Median length of follow-up (months)	32.6 ± 14.6	16.5 ± 10.4	.04
Thymoma recurrence, n (%)	1 (3.4%)	0 (0)	1

Data are represented as mean ± SD or number (percentage).

FEV1, forced expiratory volume in 1 second; S-VATT, subxiphoid video-assisted thoracoscopic thymectomy; T-VATT, transthoracic video-assisted thoracoscopic thymectomy.

The surgical outcomes in the T-VATT and S-VATT groups are presented in Table 2. All surgeries were performed under thoracoscopy with no conversion. There were no significant differences in the mean operative time between the groups (114.87 ± 48.71 versus 95.78 ± 46.77, P = .053). The operative blood loss (112.14 ± 117.01 versus 58.81 ± 48.67, P = .003), duration of chest tube usage (3.77 ± 1.83 versus 2.18 ± 1.88, P = .000), postoperative pain score (4.99 ± 0.99 versus 1.57 ± 0.55, P = .000), and length of postoperative hospital stay (5.83 ± 1.38 versus 4.38 ± 1.26, P = .000) were significantly more favorable in the S-VATT group than in the T-VATT group.

Table 2.

Comparison of Operative Outcomes

Variable	T-VATT (n = 70)	S-VATT (n = 37)	P
Conversion	0	0
Operative time (minutes)	114.87 ± 48.71	95.78 ± 46.77	.053
Operative blood loss (mL)	112.14 ± 117.01	58.81 ± 48.67	.003
Duration of chest tube (days)	3.77 ± 1.83	2.18 ± 1.88	.000
Postoperative pain score	4.99 ± 0.99	1.57 ± 0.55	.000
Postoperative hospital stay (days)	5.83 ± 1.38	4.38 ± 1.26	.000

Data are represented as mean ± SD or number.

S-VATT, subxiphoid video-assisted thoracoscopic thymectomy; T-VATT, transthoracic video-assisted thoracoscopic thymectomy.

In this cohort, 44 patients were diagnosed with MG (Table 3). MG was diagnosed by a neurologist, and the patients were examined with acetylcholine receptor (AChR) antibody analysis and chest CT scans; 16 of these patients underwent S-VATT and 28 T-VATT. The MGFA clinical classification scheme and QMG scoring systems were used to assess clinical severity and surgical outcomes.¹¹ In the T-VATT group, the median operative time was 141.46 minutes, which was significantly longer than that in the S-VATT group (median 95.63 minutes, P = .004). The S-VATT group also had significantly less intraoperative blood loss, lower postoperative pain scores, earlier chest tube removal, and a shorter postoperative hospital stay. No patients in either group developed a preoperative MG crisis. Improvement or no change in QMG was observed in all patients. The dose reduction of cholinesterase inhibitors did not differ significantly between the two groups (Table 3).

Table 3.

Perioperative Characteristics of Patients with Myasthenia Gravis

Variable	T-VATT (n = 28)	S-VATT (n = 16)	P
Age (years)	46.25 ± 16.71	53.13 ± 14.01	.17
Male/female	13/15	6/10
Mortality	0	0
MGFA classification			.77
I	14	10
II	8	4
III	5	2
IV	1	0
V	0	0
Preoperative MG-QMG	3	4	.56
Approach laterality
Right	22	–
Left	0	–
Both side	6	–
Preoperative medication
CI	28	16
CI+ IVIg	14	6
AChR antibodies+	28	16
Operative time (minutes)	141.46 ± 54.17	95.63 ± 31.25	.004
Operative blood loss (mL)	151.78 ± 146.47	64.37 ± 52.65	.027
Duration of chest tube (days)	4.07 ± 1.08	2.43 ± 1.96	.001
Postoperative pain score	4.86 ± 1.11	1.62 ± 0.62	.000
Postoperative hospital stay (days)	5.75 ± 0.84	3.94 ± 1.61	.000
Improvement or stable of MG-QMG score	28 (100%)	16 (100%)
Dose reduction of cholinesterase inhibitors	23 (82.1%)	13 (81.3%)	1

Data are represented as mean ± SD or number (percentage).

AChR, acetylcholine receptor; CI, cholinesterase inhibitors; IVIg, intravenous immunoglobulin; MGFA, Myasthenia Gravis Foundation of America; QMG, Quantitative Myasthenia Gravis; S-VATT, subxiphoid video-assisted thoracoscopic thymectomy; T-VATT, transthoracic video-assisted thoracoscopic thymectomy.

Postoperative outcomes are presented in Table 4. The overall incidence of perioperative complications was not significantly different between the T-VATT and S-VATT groups (7.1% versus 10.8%, P = .71). In the T-VATT group, 2 patients developed pneumonia and 3 patients developed arrhythmia; in the S-VATT group, 3 patients developed paralysis of the left phrenic nerve and 1 had delayed wound healing.

Table 4.

Comparison of Postoperative Outcomes

Variable	T-VATT (n = 70)	S-VATT (n = 37)	P
Mortality	0	0
Postoperative complications	5 (7.1%)	4 (10.8%)	.71
Crisis	0	0
Paralysis of LPN	0	3
Pneumonia	2	0
Arrhythmia	3	0
Delayed wound healing	0	1

LPN, left phrenic nerve; S-VATT, subxiphoid video-assisted thoracoscopic thymectomy; T-VATT, transthoracic video-assisted thoracoscopic thymectomy.

Discussion

Thymectomy is considered the cornerstone treatment for thymoma, anterior mediastinal tumors, and MG.¹² Due to its technical advantages and superior oncological results, transsternal thymectomy is considered to be the gold standard for resection surgeries.^13,14 In recent years, minimally invasive techniques for thymectomy have been accepted as an alternative approach because these approaches can ensure complete tumor removal and avoid the disadvantages of open surgery.^15–17

However, the oncological efficacy of minimally invasive thymectomy is still controversial. The thoracoscopic technique may increase the risk of capsular disruption, pleuropericardial, seeding or incomplete resections, leading to locoregional recurrence.¹⁴ For the thymoma patients in both groups, we followed the principles of minimally invasive resection published by the International Thymic Malignancy Interest Group¹⁶: resection of thymoma, thymus, and mediastinal fat; dissection and visualization of the innominate vein and both phrenic nerves; removal of the specimen in a bag; and examination of the removed specimen to ensure completeness of the resection. We chose early-stage thymoma patients who underwent minimally invasive thymectomy. In this study, all thymomas in both groups were Masaoka stage I-II; no cases of Masaoka stage III-IV or thymic carcinoma were included. None of the 37 patients had an incomplete resection or capsular disruption. Due to the short follow-up period, the locoregional recurrence and oncological outcomes are still unclear.

T-VATT has been the most frequently performed minimally invasive approach since 1993.¹⁸ The drawback of this approach is difficulty in intraoperative resection of the cervical thymus and contralateral thymus. With this approach, surgery begins by inserting two to three ports into the intercostal spaces in the lateral aspect of the chest. However, as inserting the port through intercostal spaces is associated with the possibility of intercostal nerve damage, a portion of patients who undergo this approach develop intercostal nerve paralysis or post-thoracotomy pain syndrome.¹⁹

S-VATT was first reported in 1999 by Kido et al.²⁰ This subxiphoid approach can provide a good surgical view of the upper pole of the thymus, bilateral cardiophrenic angle fat, and bilateral phrenic nerves.²¹ Multiportal or uniportal approach subxiphoid thymectomy with or without technique was reported showing a worldwide interest in the issue of minimally invasive surgery.^6,7,15 However, complicated surgical procedures or large thymic tumors should be limited due to the inadequate surgical manipulability of this subxiphoid approach. Compared with other subxiphoid methods, the subxiphoid approach with two additional small subcostal incisions can avoid interference among the surgical instruments and make the surgical procedure with comparative ease. In this cohort, the volume of blood loss, duration of chest tube usage, length of postoperative hospital stay, and postoperative pain scores were significantly more favorable in the S-VATT group than in the T-VATT group. However, the mean operative time was similar between the two groups. This result may be due to the learning curve of S-VATT. In MG patients, the surgery includes thymectomy and anterior mediastinal fat dissection. The mean operative time in the S-VATT group was clearly shorter than that in the T-VATT group. A total of 6 patients underwent bilateral transthoracic thymectomy, and the surgical approach from both the right and left sides increased the operative time.

In this study, differences in postoperative complications between the groups were not significant. The complication rate was 7.1% (5/70) in the T-VATT group and 10.8% (4/37) in the S-VATT group. Five patients in the T-VATT group had the following major complications: 2 pneumonia and 3 arrhythmia. Four patients in the S-VATT group presented with complications: 3 paralysis of left phrenic nerve and 1 delayed wound healing. Three patients experienced transient cardiac arrhythmia in the T-VATT group after surgery, including 2 cases of atrial fibrillation and 1 case of tachycardia. Two cases with postoperative pneumonia recovered fast after antibiotics were used. The most common complications in the T-VATT group were pneumonia and arrhythmia. In the S-VATT group, there were 3 cases of paralysis of the left phrenic nerve, all of which occurred in the early stage. One case resulted from the tumor being located near the phrenic nerve, and the phrenic nerve was injured during mobilization of the tumor. The 2 other patients had obesity, and it was difficult to distinguish the phrenic nerve, which was surrounded by the fat pad. During the follow-up, the patients were not in need of future medical treatment. Thus, surgeons should pay more attention to patients with obesity when using this subxiphoid approach because of the excessive anterior mediastinal fat, which may affect the surgical view. In the T-VATT group, we typically performed thymectomy from the right side; thus, it is difficult to expose and damage the left phrenic nerve. Nonetheless, there was a better surgical view of the left phrenic nerve in the S-VATT group. Occasionally, a clear view of the left phrenic nerve cannot be achieved in patients with morbid obesity. In this situation, it is easy to damage the left phrenic nerve, especially during extended thymectomy.

MG is a disorder of neuromuscular transmission that results from the binding of autoantibodies to components of the neuromuscular junction, most commonly the AChR.²² The use of thymectomy in patients with MG began in the 1940s,²³ and the principle of thymectomy for MG is based on the central role of the thymus in the pathogenesis of the disease.²⁴ Hyperplastic thymus and thymoma are the most common pathological findings in patients with MG.²⁵ Wolfe and colleagues reported a randomized, medication-controlled, rater-blinded clinical trial in 2016, in which they concluded that in patients with non-thymomatous MG, thymectomy improved clinical outcomes over a 3-year period.²⁶ However, the surgical approach in this study was standard median sternotomy. The concern of the minimally invasive procedure for thymectomy is incomplete resection of ectopic thymic tissue. It is difficult to expose and resect the tissues that are located in the contralateral peri-phrenic and pericardial fields. Some series have reported that the VATS procedure is superior to sternotomy in terms of invasiveness and efficacy for MG.^27–29 The subxiphoid approach can overcome this limitation. No crisis was observed in our cohort, and MG-QMG scores did not worsen after thymectomy in either group. There were 81.3% cases with a dose reduction of cholinesterase inhibitors in the S-VATT group compared with 82.1% in the T-VATT group. Our data indicate that the efficacy of extended thymectomy using a subxiphoid approach is not inferior to that of extended thymectomy using a transthoracic approach. The long-term remission rate of MG is still unclear, and further study is needed.

Limitations

The primary limitation of this study is its retrospective nature. All patients were recruited from one hospital; thus, intrinsic bias may exist, including with regard to the surgeons' preferences and learning curves for S-VATT. We did not perform propensity score matching due to the small sample size and because we wanted to present the real situations of thymectomy in our hospital. Nonetheless, the sample size of this study was small, which may influence the results. In addition, as long-term follow-up was not performed, the oncological results of these two groups remain unclear. Further studies with larger case series and longer follow-ups should be conducted to assess the safety and oncological efficacy of the subxiphoid approach.

Conclusion

Subxiphoid video-assisted thoracic surgery is a safe approach for patients with thymic diseases and has potential advantages of a shorter operative time, less intraoperative bleeding and less postoperative pain when compared with the lateral transthoracic approach, especially for patients with MG.

Footnotes

Disclaimer

The authors declare that the work described was original research, which has not been published previously, and is not under consideration for publication elsewhere, in whole or in part. All of the authors listed have approved the enclosed article.

Authors' Contributions

H.X. participated in writing the article; D.L. collected data; Y.L., L.Y., F.W., and W.W. participated in surgery; and L.Z. designed the work.

Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was provided for this work.

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